Alkylgermasesquioxide Derivatives of tert-Butyl-diacylhydrazines

Article abstract of DOI:10.1002/hc.10174

N-tert-Butyl-N-benzoylhydrazine was synthesized by a new method. Its condensation and the condensation of its N,N'-isomer with 3-(trichlorogermyl)propionyl chloride provided N-tert-butyl-N'-(3-trichlorogermyl)propionyl-N-benzoylhydrazine or its N,N,N'-isomer, respectively, in good yields. Subsequent hydrolysis of the trichlorogermyl compounds using saturated sodium carbonate yielded the corresponding germasesquioxide derivatives that have good solubility in organic solvents. The structures of these compounds were confirmed by 1H NMR, IR, MS, and elemental analysis. The hydrolysis of organogermanium trichloride was studied, and the elimination of HGeCl3 was observed when the basicity was too high (pH>10).

Full text of DOI:10.1002/hc.10174

Heteroatom Chemistry
Volume 14, Number 4, 2003
Alkylgermasesquioxide Derivatives
of tert-Butyl-diacylhydrazines
Qingmin Wang and Runqiu Huang
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic
Chemistry, Nankai University, Tianjin 300071, People’s Republic of China
Received 10 February 2003; revised 10 March 2003
premature molting [1–3]. Relationships between the
ABSTRACT: N-tert-Butyl-N-benzoylhydrazine was
structure and biological activity of the N-tert-butyl-
synthesized by a new method. Its condensation and
N,Nꢀ-dibenzoylhydrazine larvicides have been exten-
the condensation of its N,Nꢀ-isomer with 3-(trichloro-
sively investigated. The results indicated that the
germyl)propionyl chloride provided N-tert-butyl-Nꢀ-(3-
molecular hydrophobicity is favorable [4–6]. In ad-
trichlorogermyl)propionyl-N-benzoylhydrazine or its
dition, germasesquioxide compounds have recently
N,N,Nꢀ-isomer, respectively, in good yields. Subse-
attracted considerable attention because of their un-
quent hydrolysis of the trichlorogermyl compounds
usual physical and chemical properties and marked
using saturated sodium carbonate yielded the cor-
biological activities [7–14]. It is conceivable that the
responding germasesquioxide derivatives that have
incorporation of the two moieties into one structural
good solubility in organic solvents. The structures
unit might produce an unexpected effect on the bi-
of these compounds were confirmed by 1H NMR,
ological activity. Therefore, we designed and synthe-
IR, MS, and elemental analysis. The hydrolysis of
sized the novel diacylhydrazines containing a ger-
organogermanium trichloride was studied, and the
masesquioxide group.
elimination of HGeCl3was observed when the basicity
ꢁ
C
was too high (pH > 10).
2003 Wiley Periodicals, Inc.
RESULTS AND DISCUSSION
Heteroatom Chem 14:293–297, 2003; Published online
in Wiley InterScience (www.interscience.wiley.com). DOI
10.1002/hc.10174
N-tert-Butyl-N-benzoylhydrazine (3) is an impor-
tant intermediate in the synthesis of N-tert-butyl-
N,Nꢀ-dibenzoylhydrazine derivatives and three
synthesizing methods have been published: (1)
N-tert-Butylhydrazine was reacted with di-tert-
butyldicarbonate to afford N-tert-butyloxycarbonyl-
Nꢀ-tert-butylhydrazine, and then condensation
with benzoyl chloride and deprotection using
hydrochloric acid yielded 3 in 38% yield [15];
(2) N-tert-Butylhydrazine was reacted with N-(9-
fluorenylmethylcarbonyl)succinimide to afford N-
tert-butyl-Nꢀ-(9-fluorenylmethylcarbonyl)hydrazine,
and then acylation and deprotection using
piperidine provided 3 [16]; (3) N-tert-Butyl-Nꢀ-
acetonehydrazone was condensed with benzoyl
chloride, and then deprotection using hydrochloric
acid afforded 3 [17]. However, all of these methods
have some problems. In the methods (1) and
(3), the yields are low (<50%). Method (2) is
INTRODUCTION
Recently, a new class of insect growth regulators, the
N-tert-butyl-N,Nꢀ-diacylhydrazines, has been found
to mimic the action of 20-hydroxyecdysone in ac-
tivating the ecdysone receptor, leading to lethal
Correspondence to: Runqiu Huang; e-mail: wang98h@263.net.
Contract grant sponsor: National Natural Science Foundation
of China.
Contract grant number: 20202005.
Contract grant sponsor: Research Fund for the Doctoral
Program of Higher Education.
Contract grant number: 20010055006.
Contract grant sponsor: Foundation of National Excellent
Doctoral Dissertation of P.R. China.
c
ꢁ
2003 Wiley Periodicals, Inc.
293

294 Wang and Huang
not economical, because the expensive N-(9-fluo-
renylmethylcarbonyl)succinimide is used. Herein
we report the synthesis of 3 by a novel procedure.
Phenyl chloroformate was treated with tert-
butylhydrazine hydrochloride to obtain N-tert-butyl-
Nꢀ-phenoxycarbonylhydrazine (1), and subsequent
acylation with benzoyl chloride yielded N-tert-
butyl-Nꢀ-phenoxycarbonyl-N-benzoylhydrazine (2).
Deprotection using sodium hydroxide provided 3, as
shown in Scheme 1. This method has a number of ad-
vantages: The reaction is carried out under mild con-
ditions, starting materials are easily prepared, and
the experimental procedure is very simple. Because
of its simplicity and high efficiency, this method has
already been applied to the preparation of N-tert-
butyl-N-benzoylhydrazines in our laboratory.
Benzoyl and 4-chlorobenzoyl chloride were con-
densed with tert-butylhydrazine hydrochloride to
give Nꢀ-tert-butyl-N-benzoylhydrazines (4) in good
yields, as shown in Scheme 2.
3-Phenyl-3-(trichlorogermyl)propionyl chloride
(5) was condensed with 3 to give N-tert-butyl-Nꢀ-(3-
phenyl-3-trichlorogermyl)propionyl- N-benzoylhyd-
razine (6a) in 82% yield. Subsequent hydrolysis of
the trichlorogermyl compound 6a using saturated
sodium carbonate yielded the corresponding ger-
masesquioxide derivative 7a, as shown in Scheme
3. The compounds 6b–c and 7b–c were similarly
prepared (Scheme 4).
SCHEME 2
of condensation and solubility of germasesquioxide
resulting from the hydrolysis of the organogerma-
nium trichlorides. When the pH value of the solu-
tion is large, the condensation is small and solubil-
ity of germasesquioxide is acceptable. We found that
the hydrolysis of trichlorogermyl derivatives (6a–c)
was carried out with saturated sodium carbonate
1
to give germasesquioxides 7a–c. H NMR, IR, and
elemental analysis data supported the structure of
the compound 7. All germasesquioxides 7a–c melt
below 300◦C. The IR spectra (KBr) of 7a–c have
a strong absorption (800–900 cm−1), characteristic
of germanium–oxygen bonds [18,19]. A strong and
broad absorption (3100–3500 cm−1) attributable to
Ge OH species is noted. In 1H NMR spectra of 7a–c,
the proton of group GeOH gives rise to a signal in the
range of δ 1.5–4.0 ppm [20,21].
In conclusion, a new method for the synthesis
of N-tert-butyl-N-benzoylhydrazine enjoys a num-
ber of advantages. Hydrolysis of organogermanium
trichlorides using saturated sodium carbonate yield
germasesquioxides that have good solubility in or-
ganic solvents. The hydrolysis of organogermanium
trichloride was studied. Elimination of HGeCl3 from
trichlorogermyl derivatives was observed for the first
time when the basicity was too high (pH > 10).
We found that the hydrolysis of trichlorogermyl
derivatives (6a–c) must be carried out with satu-
rated sodium carbonate. When the acidity is too
high (pH < 7), the hydrolysis of organogermanium
trichlorides is incomplete; when the basicity is too
high (pH > 10), HGeCl3 can eliminate and a by-
product 8 is formed, as shown in Scheme 5. This
elimination of HGeCl3from trichlorogermyl deriva-
tives was observed for the first time. Moreover, the
pH value of the solution may affect the degree
EXPERIMENTAL
Proton NMR spectra were obtained at 200 MHz us-
ing a Bruker AC-P 200 spectrometer. Chemical shifts
SCHEME 1
SCHEME 3

Alkylgermasesquioxide Derivatives of tert-Butyl-diacylhydrazines 295
1
solid in 71% yield, mp 106–108◦C. H NMR (CDCl3,
200 MHz) δ: 1.12 (s, 9H, But), 5.14 (br, 2H, NHNH),
7.08–7.56 (m, 5H, Ph).
N-tert-Butyl-Nꢀ-phenoxycarbonyl-N-
benzoylhydrazine (2)
A solution of benzoyl chloride (0.054 mol) in methy-
lene dichloride (15 ml) was added dropwise to a so-
lution of 1 (0.054 mol) and triethylamine (0.065 mol)
in methylene dichloride (40 ml) under magnetic stir-
ring at 0◦C. The resulting mixture was then stirred
at room temperature for 2 h. The solid was filtered
off and the filtrate was washed successively with 2%
aqueous hydrochloric acid and 10% aqueous sodium
bicarbonate, and dried with anhydrous magnesium
sulfate and filtered. The solvent was removed by dis-
tillation to give a white solid. The solid was then re-
crystallized from ethanol to obtain a colorless crys-
SCHEME 4
(δ) are given in ppm. Infrared spectra were recorded
on a Shimadzu-435 spectrometer. Elemental analy-
ses were determined on an MT-3 elemental analyzer.
Melting points were taken on a Thomas–Hoover
melting point apparatus and are uncorrected. Mass
spectra were recorded with HP 5988A spectrometer
using the EI method.
1
talline solid in 81% yield, mp 141–143◦C. H NMR
(CDCl3, 200 MHz) δ: 1.40 (s, 9H, But), 6.74–7.32 (m,
10H, Ph).
N-tert-Butyl-N-benzoylhydrazine (3)
Compound 2 (8.00 mmol) was dissolved in luke-
warm ethanol (40 ml). While the reaction mixture
was stirred, a 15% aqueous solution of sodium hy-
droxide (50 ml) was added. Following the addition,
the mixture was stirred at 60◦C for 1 h. It was then
cooled and extracted three times with 100 ml of chlo-
roform. The extraction solvent was dried with anhy-
drous magnesium sulfate and filtered. The solvent
was removed by distillation to give a white solid. The
solid was then recrystallized from isopropanol and
petroleum ether to obtain a colorless crystalline solid
N-tert-Butyl-Nꢀ-phenoxycarbonylhydrazine (1)
To a mechanically stirred suspension of tert-
butylhydrazine hydrochloride (0.092 mol) in toluene
(100 ml) was added dropwise a solution of 10% aque-
ous sodium hydroxide (0.092 mol) at room tem-
perature. After 15 min, the reaction mixture was
cooled to −15◦C, and solutions of phenyl chloro-
formate (0.088 mol) in toluene (30 ml) and 10%
aqueous sodium hydroxide (0.088 mol) were added
dropwise and simultaneously from separate addition
funnels, while maintaining the temperature below
−10◦C. Following the addition, the reaction mixture
was warmed to room temperature and stirred for
2 h. The water phase was extracted three times with
100 ml of chloroform. The extraction solvent was
combined with the organic phase, and dried with
anhydrous magnesium sulfate and filtered. The sol-
vent was removed by distillation to give a white solid.
The solid was then recrystallized from isopropanol
and petroleum ether to obtain a colorless crystalline
1
in 76% yield, mp 127–129◦C. H NMR (CDCl3, 200
MHz) δ: 1.48 (s, 9H, But), 3.90 (s, 2H, NH2), 7.28–
7.56 (m, 5H, Ph). IR (KBr): 3276.0 (NH2), 1620.5
(C O), 1573.1, 1529.5, 1508.8 (Ph), 1375.6, 1350.0
(But), 719.6, 696.7 (Ph) cm−1.
Nꢀ-tert-Butyl-N-substituted
Benzoylhydrazines (4)
Nꢀ-tert-Butyl-N-benzoylhydrazine (4a) was prepared
similar to 1. Yield: 91%, mp 92–94◦C (Ref. [22], Yield:
54%, mp 92–94◦C)
Nꢀ-tert-Butyl-N-(4-chlorobenzoyl)hydrazine (4b)
was prepared similar to 4a. Yield: 98%, mp 118–
120◦C (Ref. [22], mp 116–122◦C).
3-Phenyl-3-(trichlorogermanyl)propionyl
Chloride (5)
3-Phenyl-3-(trichlorogermanyl)propionyl chloride
SCHEME 5
(5) was prepared according to the reported

296 Wang and Huang
procedure [23–25]. Yield: 86%, bp 124–126◦C/
0.3 mmHg (Ref. [23–25], Yield: 83%, bp 118–119◦C/
0.2 mmHg).
3-(Trichlorogermanyl)propionyl chloride was
prepared similar to 5. Yield: 93%, bp 90–91◦C/
4 mmHg (Ref. [23–25], Yield: 89%, bp 109◦C/
10 mmHg).
Compound 7a
To a solution of the compound 6a (2.5 mmol) in
methylene dichloride (10 ml), a saturated solution of
sodium carbonate was added with vigorous stirring.
After the addition, the resulting mixture was stirred
at room temperature for 12 h. The water phase was
extracted three times with 20 ml of methylene dichlo-
ride. The extraction solvent was combined with the
organic phase. The solvent was removed by distilla-
tion to give a white solid. The solid was then washed
successively with distilled water and ether. Finally,
a white powder 7a was obtained. Yield: 90%, mp
Compound 6a
A mixture of N-tert-butyl-N-benzoylhydrazine (3)
(2.5 mmol), triethylamine (3.0 mmol), and methy-
lene dichloride (20 ml) was stirred in an ice-salt bath,
and then a solution of 5 (2.5 mmol) in 10 ml of methy-
lene dichloride was added dropwise at 0◦C. After the
solution had been stirred at 0◦C for 1 h and then
at ambient temperature for 10 h, the solid was fil-
tered off and the filtrate was washed with hydrochlo-
ric acid. The washed solution was dried with anhy-
drous magnesium sulfate and filtered. The solvent
was removed by distillation to give a white solid.
The solid was then recrystallized from methylene
dichloride and petroleum ether to obtain a colorless
1
212–214◦C. H NMR (CF3CO2D, 200 MHz) δ: 1.38
(s, 9H, But), 2.06 (m, 2H, CH2C O), 3.36 (m, 1H,
CHGe), 3.60 (br, 1H, GeOH), 6.80–7.68 (m, 10H,
Ph). IR (KBr): 3404.0, 1685.5, 1634.5, 1381.4, 1364.0,
875.0, 757.9, 694.5, 658.2, 585.9 cm−1. Anal. Calcd for
C20H26GeN2O5: C, 53.70; H, 5.86; N, 6.27. Found: C,
53.86; H, 5.49; N, 6.54.
7b and 7c were prepared similar to 7a.
Compound 7b
1
crystalline solid 6a. Yield: 82%, mp 201–203◦C. H
Yield: 90%, mp 180–192◦C. 1H NMR (CF3CO2D,
200 MHz) δ: 1.46 (s, 9H, tBu), 2.12 (m, 2H, CH2CO),
3.12 (br, 1H, GeOH), 3.76 (m, 1H, CHGe), 7.04–
7.86 (m, 10H, Ph). IR (KBr): 3393.0, 3053.5, 2916.0,
1665.4, 1608.7, 1579.8, 1518.2, 1481.4, 1450.8,
1389.3, 1362.3, 1272.7, 1235.4, 1210.4, 1185.0,
1069.1, 1023.0, 867.6, 804.3, 772.0, 692.6, 646.7,
459.3 cm−1. Anal. Calcd for C20H24GeN2O4: C, 55.99;
H, 5.63; N, 6.52. Found: C, 56.07; H, 6.00; N,
6.43.
NMR (CDCl3, 200 MHz) δ: 1.48 (s, 9H, But), 2.04
(m, 2H, CH2C O), 3.50 (m, 1H, CHGe), 7.00–7.68
(m, 10H, Ph), 6.56 (br, 1H, NH). IR (KBr): 3180.0,
1660.0, 1628.7, 1396.6, 1363.7, 750.2, 692.4, 656.3,
523.2 cm−1. Anal. Calcd for C20H23Cl3GeN2O2: C,
47.81; H, 4.61, N, 5.57. Found C, 47.83, H, 4.61, N,
5.84.
6b and 6c were prepared similar to 6a.
Compound 6b
Yield: 83%, mp 160–162◦C. 1H NMR (CDCl3,
Compound 7c
3
200 MHz) δ: 1.57 (s, 9H, But), 3.16 (d, 2H, JHH
=
Yield: 88%, mp 252–300◦C. 1H NMR (CF3CO2D,
200 MHz) δ: 1.42 (s, 9H, But), 2.10 (m, 2H, CH2Ge),
3.00 (m, 3H, CH2C O, GeOH), 7.42, 7.66 (dd,
6.2 Hz, CH2C O), 3.66 (m, 1H, CHGe), 7.12–7.78 (m,
10H, Ph), 8.12 (br, 1H, NH). IR (KBr): 3140.0, 1656.0,
1607.0, 1394.4, 1364.3, 763.2, 695.9, 649.4, 517.6
cm−1. Anal. Calcd for C20H23Cl3GeN2O2: C, 47.81, H,
4.61, N, 5.57. Found: C, 47.92; H, 4.90; N, 5.53. EIMS
m/z (%): 502.25 (M+, 1), 192.40 (100), 177.30 (39),
136.30 (57), 131.30 (14).
3
4H, JHH = 8.00 Hz, Ph). IR (KBr): 3400.0, 1658.7,
1594.4, 1384.0, 1363.4, 862.8, 842.0, 692.7, 522.3
cm−1. Anal. Calcd for C14H19ClGeN2O4: C, 43.41;
H, 4.94; N, 7.23. Found: C, 42.99; H, 4.97; N,
7.13.
Compound 6c
Compound 8
Yield: 79%, mp 204–205◦C. 1H NMR (CDCl3,
A colorless crystalline solid, mp 186–188◦C. 1H NMR
(CDCl3, 200 MHz) δ: 1.50 (s, 9H, But), 6.78 (d, 1H,
3 JHH = 15.6 Hz, C CH), 7.52 (d, 1H, 3 JHH = 15.6 Hz,
200 MHz) δ: 1.50 (s, 9H, But), 2.18 (m, 1H, CH2Ge),
3
2.82 (m, 2H, CH2C O), 7.49, 7.73 (dd, 4H, JHH
=
8.50 Hz, Ph), 7.89 (br, 1H, NH). IR (KBr): 3229.5,
1658.0, 1602.2, 1396.7, 1367.5, 841.9, 671.8, 527.9
cm−1. Anal. Calcd. for C14H18Cl4GeN2O2: C, 36.49; H,
3.93; N, 6.08. Found: C, 36.38; H, 3.63; N, 5.99.
C CH), 7.21–7.86 (m, 10H, Ph), 9.14 (br, 1H, NH).
Anal. Calcd for C20H22N2O2: C, 74.51; H, 6.88; N, 8.69.
Found: C, 74.60; H, 6.48; N, 8.39. IR (KBr): 3219
(NH), 3072 (C H), 1683 (C 0), 1664 (C C), 1633

Alkylgermasesquioxide Derivatives of tert-Butyl-diacylhydrazines 297
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